Asparaginase Encapsulated in Erythrocytes for Patients With ALL and Hypersensitivity to PEG-asparaginase

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

Single-Arm PharmacoKinetic/PharmacoDynamic and Safety Study of Eryaspase (GRASPA®) for Patients With Hypersensitivity to PEG-Asparaginase, Diagnosed With Ph(-) Acute Lymphoblastic Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03267030
• Other study ID #: NOR-GRASPALL 2016
• Secondary ID: 2016-004451-70
• Status: Completed
• Phase: Phase 2
• Start date: August 23, 2017
• Est. completion date: October 22, 2020

Study information

• Verified date: August 2023
• Source: Aarhus University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Pegylated-asparaginase (PEG-ASP) is an important part of the treatment of childhood acute lymphoblastic leukaemia (ALL). Unfortunately 13% of patients develops allergy and further treatment is impossible. Furthermore, 6% of patients have developed antibodies (silent inactivation) and have no effect of the PEG-ASP treatment. Truncated asparaginase therapy is associated with inferior event-free survival outcomes, in particular relapse in central nervous system (CNS). Eryaspase is a new formulation of asparaginase encapsulated in erythrocytes. The erythrocyte membrane protects asparaginase against fast degradation and elimination processes. The encapsulation eliminates the direct somatic contact, and it is hypothesized that this provides the potential to prolong the activity of the enzyme and reduce toxicities.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: October 22, 2020
• Est. primary completion date: August 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 45 Years

Eligibility

Inclusion Criteria:

1. Male or female aged 1-45 years at diagnosis of ALL.

2. First line non-high risk ALL patients enrolled in NOPHO ALL2008 or ALLTogether pilot protocols including PEG-ASNase regimen.

3. Documented hypersensitivity reaction to PEG-ASNase with either:

Clinical allergy to PEG-ASNase (mild/severe). Serum ASNase activity below the lower level of quantification.

4. Karnofsky/Lansky score =50.

5. Ability to understand and willingness to sign a written ICF and to comply with the scheduled visits, treatment plans, laboratory tests and other study procedures. For patients under 18 years of age, either both parents or the legally appointed representatives had to provide consent.

Exclusion Criteria:

1. Philadelphia chromosome positive ALL.

2. Participation in another clinical trial interfering with the study therapy with exception of NOPHO ALL-2008 or ALLTogether pilot protocol. Patients can participate in other clinical trials not interfering with the study drug. In case of doubt this is assessed by the PI.

3. Uncontrolled intercurrent illness including, but not limited to, patients receiving combination antiretroviral therapy or patients with severe or systemic infection, or psychiatric illness/social situations that would limit compliance with study requirements.

4. Other severe acute/chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.

5. Pregnant or lactating females (serum human chorionic gonadotropin pregnancy test at screening). Use of a highly effective contraceptive measure in women of child-bearing potential and sexually active girls that are of child-bearing potential is required (contraceptive measures are specified in section 6.0).

6. Inadequate organ functions, which prohibit further asparaginase administration;

1. History of pancreatitis

2. History of serious hemorrhage or serious thrombosis with prior asparaginase therapy

3. Severe hepatic impairment at the time of administration (bilirubin >3 times ULN, transaminases >10 times ULN)

4. Pre-existing known coagulopathy (e.g. haemophilia)

7. History of grade 3 or higher transfusion reactions or any contraindication to receive blood transfusion. Presence of specific anti-erythrocytes antibodies (auto-antibodies or anti-public antibodies) preventing from getting a compatible packed Red Blood Cells for the patient.

8. Patient under concomitant treatment likely to cause hemolysis.

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Hypersensitivity
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• GRASPA
Administration of 1-7 doses of 150 IU/kg IV infusion. (every 2 weeks for a maximum of 4 doses and every 6 weeks for maximum 3 doses).

Locations

Country	Name	City	State
Denmark	Aalborg University Hospital, pediatric department	Aalborg
Denmark	Aahus University hospial, hematological department	Aarhus	Aarhus C
Denmark	Aarhus University hospital	Aarhus	Aarhus N
Denmark	Rigshospitalet, Child and Adolescent Medicine	Copenhagen
Denmark	Rigshospitalet, Hematological department	Copenhagen
Denmark	Odense University hospital, pediatric department	Odense
Estonia	Tallin Childrens Hospital	Tallin
Estonia	Tartu University Clinics	Tartu
Finland	Childrens Hospital, Helsinki. University Central Hospital	Helsinki
Finland	Kuopio University Hospital	Kuopio
Finland	University Hospital of Oulu	Oulu
Finland	Tampere University Hospital	Tampere
Finland	Turku University Hospital	Turku
Lithuania	Vilnius University Children's Hospital	Vilnius
Norway	Helse Bergen	Bergen
Norway	Oslo Universitetssykehus, Rikshospitalet	Oslo
Norway	St Olavs Hospital	Trondheim
Sweden	Drottning Silvias Barn- och ungdomssjukhus	Göteborg
Sweden	Universitetssjukhuset Linköping	Linköping
Sweden	Skånes Universitets sjukhus	Lund
Sweden	Astrid Lindgrens Barnsjukhus Karolinska	Stockholm
Sweden	arn- och Ungdomscentrum Norrlands Universitetssjukhus	Umeå
Sweden	Akademiska sjukhuset Uppsala	Uppsala

Sponsors (2)

Lead Sponsor	Collaborator
Birgitte Klug Albertsen	ERYtech Pharma

Countries where clinical trial is conducted

Denmark,  Estonia,  Finland,  Lithuania,  Norway,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics ASNase Activity >100 U/L at 14 Days	The primary endpoint was the percentage of patients with ASNase activity >100 U/L at 14 days following the first infusion (nadir). ASNase activity >100 U/L is considered adequate for complete asparagine depletion in the blood.	14 days after first infusion
Secondary	Pharmacokinetic Parameters	Percentage of patients with ASNase activity >100 U/L at 14 days following the fourth infusion of the 2-week dosing intervals. ASNase activity >100 U/L is considered adequate for complete asparagine depletion in the blood.	14 days after fourth infusion